摘要Oroxylin A(OA),a natural compound extracted from Scutellaria baicalensis,demonstrates preventive potential against ultraviolet B(UVB)-induced non-melanoma skin cancer(NMSC),the most prevalent cancer worldwide with increasing incidence.Utilizing SKH-1 hairless mice exposed to UVB,this study showed that OA delayed NMSC onset and alleviated acute skin damage.Mechanistic investigations revealed its dual action:inhibiting inflammation and en-hancing nucleotide excision repair(NER)by stabilizing XPA,a crucial deoxyribonucleic acid(DNA)repair protein.This stabilization occurred through OA's interaction with glucose-regu-lated protein 94(GRP94),which disrupted murine double minute 2(MDM2)-mediated XPA ubiquitination and proteasomal degradation.By maintaining XPA levels,OA expedited photo-product clearance and diminished genomic instability,ultimately impeding NMSC develop-ment.These findings suggest OA as a promising chemopreventive agent targeting the GRP94/MDM2-XPA axis to counteract UVB-induced carcinogenesis.